Quality Assessment of Brain MRI Defacing Using Machine Learning.

Defacing of brain magnetic resonance imaging (MRI) scans is a crucial process in medical imaging research aimed at preserving patient privacy while maintaining data integrity. However, existing defacing algorithms are prone to errors, potentially compromising patient anonymity. This paper investigates the feasibility and efficacy of automated quality assessment for defaced brain MRIs using machine learning (ML). Our findings demonstrate the promising capability of ML models in accurately distinguishing between properly and inadequately defaced MRI scans.

Salzburg Intensive Care database (SICdb): a detailed exploration and comparative analysis with MIMIC-IV.

The utilization of artificial intelligence (AI) in healthcare is on the rise, demanding increased accessibility to (public) medical data for benchmarking. The digitization of healthcare in recent years has facilitated medical data scientists' access to extensive hospital data, fostering AI-based research. A notable addition to this trend is the Salzburg Intensive Care database (SICdb), made publicly available in early 2023. Covering over 27 thousand intensive care admissions at the University Hospital Salzburg from 2013 to 2021, this dataset presents a valuable resource for AI-driven investigations. This article explores the SICdb and conducts a comparative analysis with the widely recognized Medical Information Mart for Intensive Care - version IV (MIMIC-IV) database. The comparison focuses on key aspects, emphasizing the availability and granularity of data provided by the SICdb, particularly vital signs and laboratory measurements. The analysis demonstrates that the SICdb offers more detailed information with higher data availability and temporal resolution for signal data, especially for vital signs, compared to the MIMIC-IV. This is advantageous for longitudinal studies of patients' health conditions in the intensive care unit. The SICdb provides a valuable resource for medical data scientists and researchers. The database offers comprehensive and diverse healthcare data in a European country, making it well suited for benchmarking and enhancing AI-based healthcare research. The importance of ongoing efforts to expand and make public datasets available for advancing AI applications in the healthcare domain is emphasized by the findings.

Three-dimensional optimization of wave barriers for mitigating ground vibrations induced by underground train.

Underground train-induced vibrations can cause nearby residents discomfort, damage to buildings, and disturbance for equipment. One of the most effective ways to reduce vibrations is using wave barriers along the propagation path of the waves. Many parameters are involved in determining the efficiency of these barriers: the barrier's dimension, distance from the source of vibration, and material property, to name a few. Simultaneous study of these parameters is complex since numerical analysis of alternatives is time-consuming. Therefore, in this study, by coupling the three-dimensional finite element method and an optimization algorithm, an attempt is made to provide a comprehensive solution to find the optimal wave barriers for Tehran metro line 4 as a case study. The current study evaluates two strategies: using in-filled trenches and topology-optimized barriers. In the first strategy, results show that soft-material trenches with maximum depth close to the observation point have the best performance. Further investigations on jet grout trenches show better performance in stiffer soil and lower train speed. Using dual trenches improves performance only up to 2%, so it does not provide a suitable option. For various practical reasons, there may be no tendency to use soft-material trenches, which perform well in vibration reduction. Therefore, in the second strategy, the improvement of a hard trench (jet grout) performance by topology optimization is investigated. According to this study, topology optimization is an effective method for improving barrier performance.

Autonomous nanomanufacturing of lead-free metal halide perovskite nanocrystals using a self-driving fluidic lab.

Lead-based metal halide perovskite (MHP) nanocrystals (NCs) have emerged as a promising class of semiconducting nanomaterials for a wide range of optoelectronic and photoelectronic applications. However, the intrinsic lead toxicity of MHP NCs has significantly hampered their large-scale device applications. Copper-base MHP NCs with composition-tunable optical properties have emerged as a prominent lead-free MHP NC candidate. However, comprehensive synthesis space exploration, development, and synthesis science studies of copper-based MHP NCs have been limited by the manual nature of flask-based synthesis and characterization methods. In this study, we present an autonomous approach for the development of lead-free MHP NCs via seamless integration of a modular microfluidic platform with machine learning-assisted NC synthesis modeling and experiment selection to establish a self-driving fluidic lab for accelerated NC synthesis science studies. For the first time, a successful and reproducible in-flow synthesis of Cs3Cu2I5 NCs is presented. Autonomous experimentation is then employed for rapid in-flow synthesis science studies of Cs3Cu2I5 NCs. The autonomously generated experimental NC synthesis dataset is then utilized for fast-tracked synthetic route optimization of high-performing Cs3Cu2I5 NCs.

Low-rate smartphone videoscopy for microsecond luminescence lifetime imaging with machine learning.

Time-resolved techniques have been widely used in time-gated and luminescence lifetime imaging. However, traditional time-resolved systems require expensive lab equipment such as high-speed excitation sources and detectors or complicated mechanical choppers to achieve high repetition rates. Here, we present a cost-effective and miniaturized smartphone lifetime imaging system integrated with a pulsed ultraviolet (UV) light-emitting diode (LED) for 2D luminescence lifetime imaging using a videoscopy-based virtual chopper (V-chopper) mechanism combined with machine learning. The V-chopper method generates a series of time-delayed images between excitation pulses and smartphone gating so that the luminescence lifetime can be measured at each pixel using a relatively low acquisition frame rate (e.g. 30 frames per second [fps]) without the need for excitation synchronization. Europium (Eu) complex dyes with different luminescent lifetimes ranging from microseconds to seconds were used to demonstrate and evaluate the principle of V-chopper on a 3D-printed smartphone microscopy platform. A convolutional neural network (CNN) model was developed to automatically distinguish the gated images in different decay cycles with an accuracy of >99.5%. The current smartphone V-chopper system can detect lifetime down to ∼75 µs utilizing the default phase shift between the smartphone video rate and excitation pulses and in principle can detect much shorter lifetimes by accurately programming the time delay. This V-chopper methodology has eliminated the need for the expensive and complicated instruments used in traditional time-resolved detection and can greatly expand the applications of time-resolved lifetime technologies.

Use of a modified Burow's solution to treat canine otitis externa: A randomised comparative clinical study.

BACKGROUND: Given the increase in antimicrobial drug resistance of several pathogens that affect the ear, there is a need for alternative therapy for canine otitis externa (OE). We hypothesised that the efficacy of modified Burow's solution would be non-inferior to that of standard treatment with Surolan. METHODS: The treatment success rate of a topical aluminum acetate 2% and betamethasone 0.1% (modified Burow's) otic solution was compared with that of a standard topical otic treatment of polymyxin B sulfate, prednisolone acetate and miconazole (Surolan) suspension in a prospective, open-label clinical trial. For 10 days, 142 dogs (232 ears) with OE were treated with modified Burow's solution or Surolan. The primary study endpoint was the cure rate at 10 days. Clinical efficacy was analysed as a secondary endpoint but without assessment for non-inferiority. RESULTS: The 10-day OE cure rate was 65% and 59% in the Burow's and Surolan groups, respectively. The modified Burow's solution was non-inferior to Surolan at a non-inferiority margin of -11.5% and was more clinically effective than Surolan in dogs with OE caused by yeast or bacteria. CONCLUSION: The results of this study demonstrate that modified Burow's solution is an effective treatment for OE in dogs.

Prolonged Response to HER2-Directed Therapy in Three Patients with HER2-Amplified Metastatic Carcinoma of the Biliary System: Case Study and Review of the Literature.

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. KEY POINTS: Current guidelines recommend molecular assessment for HER2 overexpression exclusively in breast and gastric adenocarcinoma. The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 was detected and treatment with HER2-directed therapy resulted in robust responses. These cases exemplify responsiveness of non-breast/gastric histologies to HER2-directed therapies, highlighting several promising new settings for these agents. Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options.

Random matrices and condensation into multiple states.

In the present work, we employ methods from statistical mechanics of disordered systems to investigate static properties of condensation into multiple states in a general framework. We aim at showing how typical properties of random interaction matrices play a vital role in manifesting the statistics of condensate states. In particular, an analytical expression for the fraction of condensate states in the thermodynamic limit is provided that confirms the result of the mean number of coexisting species in a random tournament game. We also study the interplay between the condensation problem and zero-sum games with correlated random payoff matrices.

Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature.

The factors accounting for the pathological maintenance of a high pulmonary vascular (PV) resistance postnatally remain elusive, but neonatal stressors may play a role in this process. Cross-fostering in the immediate neonatal period is associated with adult-onset vascular and behavioral changes, likely triggered by early-in-life stressors. In hypothesizing that fostering newborn rats induces long-lasting PV changes, we evaluated them at 14 days of age during adulthood and compared the findings with animals raised by their biological mothers. Fostering resulted in reduced maternal-pup contact time when compared with control newborns. At 2 wk of age, fostered rats exhibited reduced pulmonary arterial endothelium-dependent relaxation secondary to downregulation of tissue endothelial nitric oxide synthase expression and tetrahydrobiopterin deficiency-induced uncoupling. These changes were associated with neonatal onset-increased ANG II receptor type 1 expression, PV remodeling, and right ventricular hypertrophy that persisted into adulthood. The pulmonary arteries of adult-fostered rats exhibited a higher contraction dose response to ANG II and thromboxane A2, the latter of which was abrogated by the oxidant scavenger Tempol. In conclusion, fostering-induced neonatal stress induces long-standing PV changes modulated via the renin-angiotensin system.

Membrane sorting via the extracellular matrix.

We consider the coupling between a membrane and the extracellular matrix. Computer simulations demonstrate that the latter coupling is able to sort lipids. It is assumed that membranes are elastic manifolds, and that this manifold is disrupted by the extracellular matrix. For a solid-supported membrane with an actin network on top, regions of positive curvature are induced below the actin fibers. A similar mechanism is conceivable by assuming that the proteins which connect the cytoskeleton to the membrane induce local membrane curvature. The regions of non-zero curvature exist irrespective of any phase transition the lipids themselves may undergo. For lipids that prefer certain curvature, the extracellular matrix thus provides a spatial template for the resulting lateral domain structure of the membrane.

Raft formation in lipid bilayers coupled to curvature.

We present computer simulations of a membrane in which the local composition is coupled to the local membrane curvature. At high temperatures (i.e., above the temperature of macroscopic phase separation), finite-sized transient domains are observed, reminiscent of lipid rafts. The domain size is in the range of hundred nanometers, and set by the membrane elastic properties. These findings are in line with the notion of the membrane as a curvature-induced microemulsion. At low temperature, the membrane phase separates. The transition to the phase-separated regime is continuous and belongs to the two-dimensional Ising universality class when the coupling to curvature is weak, but becomes first-order for strong curvature-composition coupling.

A lipid bound actin meshwork organizes liquid phase separation in model membranes.

The eukaryotic cell membrane is connected to a dense actin rich cortex. We present FCS and STED experiments showing that dense membrane bound actin networks have severe influence on lipid phase separation. A minimal actin cortex was bound to a supported lipid bilayer via biotinylated lipid streptavidin complexes (pinning sites). In general, actin binding to ternary membranes prevented macroscopic liquid-ordered and liquid-disordered domain formation, even at low temperature. Instead, depending on the type of pinning lipid, an actin correlated multi-domain pattern was observed. FCS measurements revealed hindered diffusion of lipids in the presence of an actin network. To explain our experimental findings, a new simulation model is proposed, in which the membrane composition, the membrane curvature, and the actin pinning sites are all coupled. Our results reveal a mechanism how cells may prevent macroscopic demixing of their membrane components, while at the same time regulate the local membrane composition. DOI: http://dx.doi.org/10.7554/eLife.01671.001.

Main transition in the Pink membrane model: finite-size scaling and the influence of surface roughness.

We consider the main transition in single-component membranes using computer simulations of the Pink model [D. A. Pink et al., Biochemistry 19, 349 (1980)]. We first show that the accepted parameters of the Pink model yield a main transition temperature that is systematically below experimental values. This resolves an issue that was first pointed out by Corvera and co-workers [Phys. Rev. E 47, 696 (1993)]. In order to yield the correct transition temperature, the strength of the van der Waals coupling in the Pink model must be increased; by using finite-size scaling, a set of optimal values is proposed. We also provide finite-size scaling evidence that the Pink model belongs to the universality class of the two-dimensional Ising model. This finding holds irrespective of the number of conformational states. Finally, we address the main transition in the presence of quenched disorder, which may arise in situations where the membrane is deposited on a rough support. In this case, we observe a stable multidomain structure of gel and fluid domains, and the absence of a sharp transition in the thermodynamic limit.

Effects of memantine on mitochondrial function.

Because NMDA complex and mitochondrial function are related, we hypothesized memantine would influence mitochondrial function. We addressed this in vitro by studying the effects of chronic and acute memantine exposures on mitochondrial function. For acute exposure experiments, mitochondria were isolated from NT2 cells and assayed for electron transport chain (ETC) enzyme function and peroxide production in buffers containing up to 60uM memantine. For chronic exposure experiments, NT2 cells were maintained for at least two weeks in medium containing up to 60uM memantine, following which we assayed cells or their mitochondria for ETC enzyme activities, cytochrome oxidase protein levels, oxidative stress, calcium levels, and mitochondrial DNA levels. The ability of the NMDA receptor antagonist aminophosphonovaleric acid (APV) to modify memantine's mitochondrial effects was evaluated. Acute and chronic memantine similarly affected complex I (increased at high concentrations) and IV (decreased at high concentrations) V(max) activities. APV did not alter the effects of chronic memantine exposure on citrate synthase and complex IV. We detected a lower mitochondrial peroxide production rate with acute exposure, and an increased mitochondrial peroxide production rate with chronic exposure. Micromolar memantine concentrations affect mitochondria, some of these effects are directly mediated, and acute and chronic effects may differ.

The thiazolidinedione pioglitazone alters mitochondrial function in human neuron-like cells.

Thiazolidinediones alter cell energy metabolism. They are used to treat or are being considered for the treatment of disorders that feature mitochondrial impairment. Their mitochondrial effects, however, have not been comprehensively studied under long-term exposure conditions. We used the human neuron-like NT2 cell line to directly assess the long-term effects of a thiazolidinedione drug, pioglitazone, on mitochondria. At micromolar concentrations, pioglitazone increased mitochondrial DNA (mtDNA) content, levels of mtDNA and nuclear-encoded electron transport chain subunit proteins, increased oxygen consumption, and elevated complex I and complex IV V(max) activities. Pioglitazone treatment was also associated with increased cytoplasmic but reduced mitochondrial peroxide levels. Our data suggest that pioglitazone induces mitochondrial biogenesis and show that pioglitazone reduces mitochondrial oxidative stress in a neuron-like cell line. For these reasons pioglitazone may prove useful in the treatment of mitochondriopathies.